MRI Keeps an Eye on Those Transplanted Stem Cells In Vivo
Quick Links
Embryonic stem (ES) cells have the inherent potential to replace or repair almost every tissue in the body. One key to this prowess is the ability to migrate, without which ES cells could not travel to the sites where they are needed. While their wanderlust may be good for health, it is problematic for researchers, who have difficulty tracking therapeutic stem cells after having implanted them into a damaged tissue or organ.
In this week's PNAS early online edition, researchers from Christian Buehrle's lab at the Max Planck Institute for Neurological Research, Cologne, Germany, describe a noninvasive method for monitoring transplanted stem cells in live rats. First author Mathias Hoehn and colleagues used a magnetic resonance imaging (MRI) technique to track stem cells implanted in the brain. The authors used cells that had been transfected with an MRI contrast agent consisting of tiny super-paramagnetic iron-oxide particles (see related news story), which allow the stem cells to be starkly visualized against the background of the host tissue.
This enhanced MRI allowed the researchers to follow the migratory patterns of cells that were transplanted into rats that had suffered stroke. ES cells that were placed into the side of the brain opposite the stroke damage were seen, after a few days, to migrate along the corpus callosum and to populate the hemisphere where the ischemia had occurred. Within two weeks, these cells spread into the lateral cortex of the damaged hemisphere while, by contrast, no migration of cells was apparent after implantation into healthy animals.
Not only does this work show that stem cells can be tracked in vivo, but as the authors point out, it also demonstrates that cerebral ischemia must trigger some signaling mechanism which, though intended for endogenous cells, can entice implanted stem cells into the damaged region.—Tom Fagan
References
Other Citations
Further Reading
No Available Further Reading
Primary Papers
- Hoehn M, Küstermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Föcking M, Arnold H, Hescheler J, Fleischmann BK, Schwindt W, Bührle C. Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16267-72. PubMed.
Annotate
To make an annotation you must Login or Register.
Comments
University of Central Florida
This is an exciting study to show in vivo migration of stem cells in the brain. I talked with the author at the Neuroscience meeting in Orlando, and was immediately impressed with their results. It shows dynamic migration of transplanted stem cells toward the lesion area, and such a pathway is exactly what we have expected based on the postmortem studies. I cannot wait to see how this technology advances clinical application of stem cell transplantation. We will be able to visualize real-time migration or distribution of transplanted cells in the live human brain.
Another group (Michel Modo et al., 2002), also published a similar technology, but they employed a slightly more elegant way, which is a combination of a MRI-enhancing molecule and a fluorescent dye molecule. This approach may be particularly useful for animal studies, where we may combine in vivo and postmortem analysis of the stem cell migration.
In any event, these technologies will become more powerful with the construction of higher-resolution (tesla) MRI machines, and more important when we get closer to the clinical application of the neural stem cell transplantation.
References:
Modo M, Cash D, Mellodew K, Williams SC, Fraser SE, Meade TJ, Price J, Hodges H. Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging. Neuroimage. 2002 Oct;17(2):803-11. PubMed.
Stem cells have the potential to treat and possibly cure a variety of disorders, particularly those of the central nervous system. To develop successful clinical therapies, the fate of these cells after grafting must be monitored in a noninvasive manner. By incorporating magnetic nanoparticles or other MR contrast agents into stem and progenitor cells, it has previously been shown that MR imaging can detect the biodistribution of these cells.(1-3) In the present paper, Hoehn and Küstermann et al. have taken this approach one step further and shown that the actual migration (i.e., movement) of transplanted mouse embryonic stem (ES) cells can be monitored in vivo. Mouse ES cells were magnetically labeled using a simple transfection method5 and transplanted in the contralateral hemisphere of rats two weeks after unilateral middle cerebral artery occlusion, an experimental model for stroke. They observed migration away from the implantation site along the corpus callosum toward the ischemic borderzone, mainly near the ventricular wall and choroid plexus. The experimental high-field MR scanner used enabled a sufficiently high resolution to detect these structures, which corresponded to the immunospecific staining for transfected GFP used as a histopathological marker. However, it is, at present, uncertain if Hoehn’s approach will be indeed applicable to the use of standard clinical MR units to detect the migration of single clusters of magnetically labeled cells. Of further interest is that the transplanted mouse ES cells appeared to have morphologically differentiated into neurons, although further characterization data on the various possible cell lineages are pending. This study is a proof of principle of the great potential of MR imaging to follow cell migration, justifying further studies on its use in future clinical stem cell transplantation protocols.
References:
Bulte JW, Zhang S, van Gelderen P, Herynek V, Jordan EK, Duncan ID, Frank JA. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15256-61. PubMed.
Bulte JW, Douglas T, Witwer B, Zhang SC, Strable E, Lewis BK, Zywicke H, Miller B, van Gelderen P, Moskowitz BM, Duncan ID, Frank JA. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol. 2001 Dec;19(12):1141-7. PubMed.
Modo M, Cash D, Mellodew K, Williams SC, Fraser SE, Meade TJ, Price J, Hodges H. Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging. Neuroimage. 2002 Oct;17(2):803-11. PubMed.
Hoehn M, Küstermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Föcking M, Arnold H, Hescheler J, Fleischmann BK, Schwindt W, Bührle C. Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16267-72. PubMed.
Frank JA, Zywicke H, Jordan EK, Mitchell J, Lewis BK, Miller B, Bryant LH Jr, Bulte JW. Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents. Acad Radiol. 2002 Aug;9 Suppl 2:S484-7. PubMed.
Make a Comment
To make a comment you must login or register.